68 results match your criteria: "Peking Union Medicine College[Affiliation]"

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Mitochondrial tRNA pseudouridylation governs erythropoiesis.

Blood

August 2024

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

Article Synopsis
  • Pseudouridine is a common RNA modification linked to various diseases, but its effects on blood cell formation (hematopoiesis) are not well understood.
  • The study focused on how impaired tRNA pseudouridylation affects red blood cell production (erythropoiesis) in a specific blood disorder called MLASA, revealing reduced mitochondrial function and anemia in models with a PUS1 mutation.
  • Treatment with rapamycin, which inhibits mTOR signaling, improved erythroid differentiation and partially alleviated anemia symptoms in MLASA patients, highlighting the importance of mitochondrial tRNA pseudouridylation in red blood cell development and possible therapies for related anemias.
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Loss of RNA-binding protein CELF2 promotes acute leukemia development via FAT10-mTORC1.

Oncogene

May 2024

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, 100142, China.

RNA-binding proteins (RBPs) are critical regulators for RNA transcription and translation. As a key member of RBPs, ELAV-like family protein 2 (CELF2) has been shown to regulate RNA splicing and embryonic hematopoietic development and was frequently seen dysregulated in acute myeloid leukemia (AML). However, the functional role(s) of CELF2 in hematopoiesis and leukemogenesis has not been fully elucidated.

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Pseudouridine synthase 1 regulates erythropoiesis via transfer RNAs pseudouridylation and cytoplasmic translation.

iScience

March 2024

State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China.

Pseudouridylation plays a regulatory role in various physiological and pathological processes. A prime example is the mitochondrial myopathy, lactic acidosis, and sideroblastic anemia syndrome (MLASA), characterized by defective pseudouridylation resulting from genetic mutations in pseudouridine synthase 1 (PUS1). However, the roles and mechanisms of pseudouridylation in normal erythropoiesis and MLASA-related anemia remain elusive.

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C1ql3 knockout affects microglia activation, neuronal integrity, and spontaneous behavior in Wistar rats.

Animal Model Exp Med

February 2024

Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Institute of Laboratory Animal Science, Peking Union Medicine College, Chinese Academy of Medical Sciences, Beijing, China.

Background: C1QL3 is widely expressed in the brain and is specifically produced by a subset of excitatory neurons. However, its function is still not clear. We established C1ql3-deficient rats to investigate the role of C1QL3 in the brain.

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Trim46 knockout impaired neuronal architecture and caused hypoactive behavior in rats.

Dev Dyn

July 2024

Beijing Engineering Research Center for Experimental Animal Models of Human Diseases, Institute of Laboratory Animal Science, Peking Union Medicine College, Chinese Academy of Medical Sciences, Beijing, China.

Background: Tripartite motif (TRIM46) is a relatively novel protein that belongs to tripartite motif family. TRIM46 organizes parallel microtubule arrays on the axons, which are important for neuronal polarity and axonal function. TRIM46 is highly expressed in the brain, but its biological function in adults has not yet been determined.

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With the outbreak of infectious diseases, more and more attention has been paid to surveillance and early warning work. Timely and accurate monitoring data is the basis of infectious diseases prevention and control. Effective early warning methods for infectious diseases can improve the timeliness and sensitivity of early warning work.

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The world has paid a heavy price for the pandemic of the emerging respiratory communicable disease, so more concern about communicable disease surveillance and early warning has been aroused. This paper briefly reviews the establishment of the surveillance and early warning system of respiratory communicable diseases in China, discusses its future development and introduces the novel surveillance methods and early warning models for the purpose of establishment of a multi-channel surveillance and multi-dimensional early warning system of communicable diseases in the future and the improvement of the prevention and control of emerging respiratory communicable diseases in China.

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A conditional knockout rat resource of mitochondrial protein-coding genes via a DdCBE-induced premature stop codon.

Sci Adv

April 2023

Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medicine College, Beijing, China.

Hundreds of pathogenic variants of mitochondrial DNA (mtDNA) have been reported to cause mitochondrial diseases, which still lack effective treatments. It is a huge challenge to install these mutations one by one. We repurposed the DddA-derived cytosine base editor to incorporate a premature stop codon in the mtProtein-coding genes to ablate mitochondrial proteins encoded in the mtDNA (mtProteins) instead of installing pathogenic variants and generated a library of both cell and rat resources with mtProtein depletion.

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Artesunate (ART), is a semi-synthetic water-soluble artemisinin derivative extracted from the plant , which is often used to treating malaria. and studies suggested it may help decrease inflammation and attenuate airway remodeling in asthma. However, its underlying mechanism of action is not elucidated yet.

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Expanding DdCBE-mediated targeting scope to aC motif preference in rat.

Mol Ther Nucleic Acids

June 2023

Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medicine College, Beijing 100021, China.

An animal model harboring pathogenic mitochondrial DNA (mtDNA) mutations is important to understand the biological links between mtDNA variation and mitochondrial diseases. DdCBE, a DddA-derived cytosine base editor, has been utilized in zebrafish, mice, and rats for tC sequence-context targeting and human mitochondrial disease modeling. However, human pathogenic mtDNA mutations other than the tC context cannot be manipulated.

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Magnetic resonance imaging (MRI) contrast agents, such as Magnevist (Gd-DTPA), are routinely used for detecting tumors at an early stage. However, the rapid clearance by the kidney of Gd-DTPA leads to short blood circulation time, which limits further improvement of the contrast between tumorous and normal tissue. Inspired by the deformability of red blood cells, which improves their blood circulation, this work fabricates a novel MRI contrast agent by incorporating Gd-DTPA into deformable mesoporous organosilica nanoparticles (D-MON).

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Introduction: There has been controversy about renin-angiotensin system (RAS) inhibition in IgAN patients with advanced (stage 4) chronic kidney disease (CKD). Therefore, we investigated the effect of RAS blockade in these patients.

Methods: Renal specimens of 50 IgAN patients who underwent renal biopsy during stage 4 CKD between 2010 and 2020, were stained using immunohistochemistry to detect the expression of RAS receptors (AT1R, AT2R, MasR, and MrgD).

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Diagnostic potential of site-specific serotransferrin N-glycosylation in discriminating different liver diseases.

Clin Chim Acta

January 2023

Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 5 Dongdan San Tiao, Beijing 100005, China. Electronic address:

Background: Altered glycosylation modulates the structure and function of disease-related proteins. The associations between serotransferrin (STF) N-glycosylation and liver diseases (LDs) have been revealed. However, how intact N-glycopeptides vary among different types of liver diseases remains unclear.

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Signal Amplification Pretargeted PET/Fluorescence Imaging Based on Human Serum Albumin-Encapsulated GdF Nanoparticles for Diagnosis of Ovarian Cancer.

ACS Biomater Sci Eng

November 2022

Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Institute of Laboratory Animal Science, Peking Union Medicine College, Chinese Academy of Medical Sciences, No. 5 Panjiayuan Nanli, Chaoyang District, Beijing100021, China.

Different modal imaging techniques could be complementary in tumor diagnosis. Human serum albumin (HSA)-encapsulated GdF nanoparticles were developed as T1 magnetic resonance imaging (MRI) contrast agents. However, no significant T1 enhancement in the tumor site of the SKOV3 human ovarian cancer xenograft tumor model was observed within 3 h after injection of tetrazine-modified GdF@HSA NPs through small-animal MRI.

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[The role and mechanism of tumor metastasis-associated gene 1 in radiosensitivity of HeLa cells].

Zhonghua Zhong Liu Za Zhi

September 2022

National Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medicine College, Beijing 100021, China.

To determine the effect of tumor metastasis-associated gene 1 (MTA1) on the sensitivity of HeLa cells to radiotherapy, and to clarify its molecular mechanism. The transcriptome differences between MTA1 knocked down Hela cells and control cells were analyzed, and the differentially expressed genes (DEGs) was used to perform Gene-Set Enrichment Analysis (GSEA) and Gene Ontology (GO) cluster analysis. Flow cytometry was used to detect apoptosis in MTA1-overexpressed HeLa cells and control cells before and after 10 Gy X-ray irradiation.

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A comparative study of mouse bone marrow mesenchymal stem cells isolated using three easy-to-perform approaches.

FEBS Open Bio

December 2022

Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China, Institute of Laboratory Animal Science, Peking Union Medicine College, Chinese Academy of Medical Sciences, Beijing, China.

Mouse bone marrow mesenchymal stem cells (mBM-MSCs) are important for preclinical tissue regeneration and repair studies. In the present study, we isolated mBM-MSCs using three easy-to-perform methods (whole bone marrow-adherent culture, density-gradient centrifugation, and bone digestion), and then compared the morphology, proliferation, differentiation, and paracrine factor profiles of the isolated mBM-MSCs. Of these three isolation methods, the bone digestion method resulted in the highest quantity of mBM-MSCs with high growth potential and moderate differentiation.

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Cardiac-specific Trim44 knockout in rat attenuates isoproterenol-induced cardiac remodeling via inhibition of AKT/mTOR pathway.

Dis Model Mech

May 2023

Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.

When pathological hypertrophy progresses to heart failure (HF), the prognosis is often very poor. Therefore, it is crucial to find new and effective intervention targets. Here, myocardium-specific Trim44 knockout rats were generated using CRISPR-Cas9 technology.

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Dilated cardiomyopathy (DCM) is a major cause of heart failure. LMNA variants contribute to 6-10% DCM cases, but the underlying mechanisms remain incompletely understood. Here, we reported two patients carrying the LMNA c.

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Pon1 Deficiency Promotes Trem2 Pathway-Mediated Microglial Phagocytosis and Inhibits Pro-inflammatory Cytokines Release In Vitro and In Vivo.

Mol Neurobiol

July 2022

Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Institute of Laboratory Animal Science, Peking Union Medicine College, Chinese Academy of Medical Sciences, Beijing, 100021, China.

Paraoxonase 1 (PON1) plays an anti-inflammatory role in the cardiovascular system. Levels of serum PON1 and polymorphisms in this gene were linked to Alzheimer's disease (AD) and Parkinson disease (PD), but its function in the neuroimmune system and AD is not clear. To address this issue, we used Pon1 knockout rats previously generated by our lab to investigate the role of Pon1 in microglia.

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TRDMT1 exhibited protective effects against LPS-induced inflammation in rats through TLR4-NF-κB/MAPK-TNF-α pathway.

Animal Model Exp Med

April 2022

Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medicine College, Beijing, China.

Background: Inflammation is a complex physiological and pathological process. Although many types of inflammation are well characterized, their physiological functions are largely unknown. tRNA aspartic acid methyltransferase 1 (TRDMT1) has been implicated as a stress-related protein, but its intrinsic biological role is unclear.

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Myocardium-specific Isca1 knockout causes iron metabolism disorder and myocardial oncosis in rat.

Life Sci

May 2022

Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China; Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medicine College, Beijing, China; National Human Diseases Animal Model Resource Center, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Peking Union Medicine College, Beijing, China. Electronic address:

Aims: Multiple mitochondrial dysfunction (MMD) can lead to complex damage of mitochondrial structure and function, which then lead to the serious damage of various metabolic pathways including cerebral abnormalities. However, the effects of MMD on heart, a highly mitochondria-dependent tissue, are still unclear. In this study, we use iron-sulfur cluster assembly 1 (Isca1), which has been shown to cause MMD syndromes type 5 (MMDS5), to verify the above scientific question.

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Due to their broad-spectrum effects and high antitumor efficacies, anthracycline-based chemotherapies are commonly prescribed in various solid and hematological malignancies. Doxorubicin (DOX) is one of the most highly used anthracyclines but has been shown to cause lethal cardiomyopathy in clinical practice. Studies have demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to rescue DOX-induced cardiomyopathy (DIC).

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Chemokine Promotes Phagocytosis Through Its Receptor CCR8 Rather than PITPNM3 in Human Microglial Cells.

J Interferon Cytokine Res

January 2022

Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Institute of Laboratory Animal Science, Peking Union Medicine College, Chinese Academy of Medical Sciences, Beijing, China.

CCL18 is a CC chemokine that exhibits diverse functions through interaction with various cell subsets with both proinflammatory anti-inflammatory properties through its receptors CCR8 (CC chemokine receptor 8) and PITPNM3 (phosphatidylinositol transfer protein 3). However, the function of CCL18 in microglia remains unclear. In this study, we show that CCL18 did not change the expression of the inflammatory factors, interleukin (IL)-1β, IL-6, tumor necrosis factor alpha (TNF-α), or inducible nitric oxide synthase (iNOS), but significantly induced expression of the macrophage markers, MRC-1 and ARG-1 M2, in a human microglial clone 3 cell line (HMC3).

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